However, there was a higher incidence of thrombocytopenia with ruxolitinib than with control treatment, according to a report by Robert Zeiser, MD, of University of Freiburg (Germany) and colleagues on behalf of the REACH2 research group. The report was published in the New England Journal of Medicine.

The REACH2 trial (NCT02913261) is a randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with investigator’s choice of therapy for control treatment using a list of nine commonly used options.

Patients were 12 years of age or older with glucocorticoid-refractory acute GVHD after allogeneic stem cell transplant. A total of 154 patients were assigned to the ruxolitinib group, and 155 patients were in the control group.

Most patients – 152 in the ruxolitinib group and 150 in the control group – received at least one dose of trial treatment.

Treatment discontinuation occurred in 72% (111/154) of patients in the ruxolitinib group and in 85% (132/155) of those in the control group. The most common reason for discontinuation was lack of efficacy (in 21% and 44%, respectively).

Outcomes

The overall response at day 28 (the primary endpoint) was significantly higher in the ruxolitinib group than in the control group (62% vs. 39%; odds ratio, 2.64; P < .001). The durable overall response at day 56 was also significantly higher in the ruxolitinib group than in the control group (40% vs. 22%; OR, 2.38; P < .001).

The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group compared with 39% in the control group.

The median failure-free survival was considerably longer with ruxolitinib than with control treatment (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non–relapse-related death, or the use of new systemic therapy for acute GVHD, 0.46).

The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (HR, 0.83).

Overall, 72 patients (47%) in the ruxolitinib group and 77 (51%) in the control group died by the data cutoff date. Most deaths were attributed to acute GVHD (22% in the ruxolitinib group and 25% in the control group).

The most common adverse events at day 28 (in the ruxolitinib and control arms, respectively) were thrombocytopenia (33% and 18%), anemia (30% and 28%), and cytomegalovirus infection (26% and 21%).

Praise for ‘successful’ randomized trial in GVHD

“The authors are to be congratulated for completing this successful randomized trial, which showed convincingly that ruxolitinib was more effective than the investigator’s choice of therapy ... in patients in whom glucocorticoid therapy had failed,” wrote Nelson Chao, MD, of Duke University in Durham, N.C., in his invited editorial.

He went on to speculate on the possible mechanism for ruxolitinib in these patients, discussing the possible role of the STAT3 and STAT1 signaling pathways.

Dr. Chao also found it “interesting that the incidence of infectious complications or relapse was apparently not greater with ruxolitinib than with control therapy,” but he noted that the total follow-up time was short.

“As with all good research, these observations raise important questions and set the stage for further work in this area,” he concluded.

The REACH2 trial was funded by Novartis. The study authors disclosed relationships with a variety of pharmaceutical companies, including Novartis. Dr. Chao reported having no relevant disclosures.